【摘要】 目的　分析家族性高胆固醇血症低密度脂蛋白受体 (LDLR)功能变化 ,寻找基因突变位点 ;阐明该基因突变类型对LDLR功能的影响。方法　患儿及其父系、母系三代共 30人检查血脂和临床表现 ,作系谱分析 ,确定该患儿符合家族性高胆固醇血症纯合子的诊断 ;培养患儿皮肤成纤维细胞 ,用受体的放射性配体结合技术 ,定量测定细胞的LDLR的功能 ;提取外周血基因组DNA对LDLR基因的相应外显子进行PCR SSCP及DNA序列分析。结果　系谱分析发现 11个杂合子及 1个纯合子 ;纯合子患儿LDLR结合功能基本正常 ,但其内移和降解功能只有正常人的 3 6 %及 1 7%;DNA测序结果证实患儿第 17外显子的第 5 99和 6 0 0密码子间插入一个碱基G ,导致框移突变 ;第 84 2密码子发生CCA→CCG的无义突变。结论　首次报道了一个新的LDLR突变位点 ;初步明确该突变位点对患者的影响较为显著。更多还原

【Abstract】 Objective To analyse the LDL receptor (LDLR) function and gene mutation in a familial hypercholesterolemia (FH) patient and illustrate the effects of gene mutation type on LDL receptor function Methods The pedigree of a FH proband was set up according to the serum lipid analysis and clinical presentations The LDLR functions of cultured fibroblasts were investigated by radiolabelled ligand method PCR SSCP and DNA sequencing were performed on the genomic DNA isolated from whole blood Results 11 heterozygotes and 1 homozygote of FH were confirmed by pedigree analysis The binding of LDL by LDLR of the proband was nearly normal while the uptake and degradation of LDL were only 3 6% and 1 7% as compared with controls A frameshift mutation resulted from a G insert in codon 599 and a null mutation caused by CCA→CCG base shift in codon 842 were found in exon 17 Conclusion A novel mutation of LDLR gene was reported This mutation may severely affect the function of LDLR更多还原